Two complete series of N-protected, monodispersed oligopeptide esters to the pentamer level from 1-aminocyclododecane-1-carboxylic acid (Ac12c), an α-amino acid conformationally constrained through C(i)/(α) ⇆ C(i)/(α) cyclization, and either L-Ala or Aib residues, along with the N-protected Ac12c homopeptide alkylamide series from monomer to trimer, have been synthesized by solution methods and fully characterized. The solution- preferred conformations of these peptides have been assessed by Fourier transform ir absorption and 1H-nmr techniques. Moreover, the molecular structures of one derivative (Z-Ac12c-OH) and three peptides [the tripeptide ester Z-L-Ala-Ac12c-L-Ala-OMe, the tripeptide alkylamide Z- (Ac12c)3-NHiPr, and the tetrapeptide ester Z-(Aib)2-Ac12c-Aib-OtBu (Aib, α-aminoisobutyric acid)] have been determined in the crystal state by x-ray diffraction. The results obtained point to the conclusion that β-bends and 310-helices are preferentially adopted by peptides based on Ac12c, the largest cycloaliphatic C-disubstituted glycine known. A comparison with the structural tendencies extracted from published works on peptides from Aib, the prototype of C-disubstituted glycines, and the other extensively studied members of the class of 1-aminocycloalkane-1-carboxylic acids (Ac(n)c, with n = 3-9), is made and the implications for the use of the Ac12c residue in the Ac(n)c scan approach of conformationally restricted analogues of bioactive peptides are briefly discussed. (C) 2000 John Wiley and Sons, Inc.
Conformational restriction through C(i)/(α) ⇆ C(i)/(α) cyclization: Ac12c, the largest cycloaliphatic C(α,α)-disubstituted glycine known
IACOVINO, Rosa;
2000
Abstract
Two complete series of N-protected, monodispersed oligopeptide esters to the pentamer level from 1-aminocyclododecane-1-carboxylic acid (Ac12c), an α-amino acid conformationally constrained through C(i)/(α) ⇆ C(i)/(α) cyclization, and either L-Ala or Aib residues, along with the N-protected Ac12c homopeptide alkylamide series from monomer to trimer, have been synthesized by solution methods and fully characterized. The solution- preferred conformations of these peptides have been assessed by Fourier transform ir absorption and 1H-nmr techniques. Moreover, the molecular structures of one derivative (Z-Ac12c-OH) and three peptides [the tripeptide ester Z-L-Ala-Ac12c-L-Ala-OMe, the tripeptide alkylamide Z- (Ac12c)3-NHiPr, and the tetrapeptide ester Z-(Aib)2-Ac12c-Aib-OtBu (Aib, α-aminoisobutyric acid)] have been determined in the crystal state by x-ray diffraction. The results obtained point to the conclusion that β-bends and 310-helices are preferentially adopted by peptides based on Ac12c, the largest cycloaliphatic C-disubstituted glycine known. A comparison with the structural tendencies extracted from published works on peptides from Aib, the prototype of C-disubstituted glycines, and the other extensively studied members of the class of 1-aminocycloalkane-1-carboxylic acids (Ac(n)c, with n = 3-9), is made and the implications for the use of the Ac12c residue in the Ac(n)c scan approach of conformationally restricted analogues of bioactive peptides are briefly discussed. (C) 2000 John Wiley and Sons, Inc.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
